Prognostic significance of leucine-rich-repeat-containing G-protein-coupled receptor 5, an intestinal stem cell marker, in gastric carcinomas

Bo Gun Jang, Byung Lan Lee, Woo Ho Kim

Cells expressing LGR5, an intestinal stem cell marker, have been suggested as cancer stem cells in human colon cancers. Previously, we discovered that LGR5-expressing cells exist in the gastric antrum and remarkably increase in number in intestinal metaplasia. In addition, most gastric adenomas contain abundant LGR5-expressing cells coexpressing intestinal stem cell signatures. However, LGR5 expression in gastric cancers (GCs) and its prognostic significance remain unknown. We examined the LGR5 expression in GC tissues by real time-PCR and RNA in situ hybridization, and analyzed its clinicopathological relevance and prognostic value. The effects of LGR5 on cancer cell proliferation and migration were assessed with an in vitro transfection technique. LGR5 expression was significantly lower in GCs than in matched nontumorous gastric mucosa. RNA in situ hybridization on tissue microarrays showed that 7 % of GCs were positive for LGR5. LGR5 positivity was associated with old age, well to moderate differentiation, and nuclear β-catenin positivity. Although LGR5 did not show any prognostic significance for all GC cases, it was associated with poor survival in GCs with nuclear β-catenin expression. LGR5 expression was induced by transfection in GC cell lines with abnormal Wnt activation, which, however, showed no influence on the growth and migration of GC cells. A small portion of GCs expressed LGR5. Although LGR5 was associated with poor survival in GCs with nuclear β-catenin, LGR5 expression in GC cells had no effects on the growth and migration, requiring a further study exploring a biological role of LGR5 in GCs.